Dream over life: Psychedelic terphenyl derivative induce hallucination via cannabinoid receptor 1

Abstract

For ages, natural psychedelic resources have been used by ancient tribes for religious inspiration. In modern medicine, these compounds were prescribed to relieve severe distress and depression on cancer patients. Despite medical benefit, abuse of these compounds have become prevalent in our modern society. These compounds usually interacted with cannabinoid receptor 1 (CNR1) on neuron cell causing hallucination, and on other cell-types. In this study, chemically synthesized terphenyl derivative, 1,4-di(phenyl)benzene (13-BPB) interaction with human and its animal model were assessed. This derivative is an analogue found in fungi although their functional molecular mechanism is unknown. Terphenyl derivative known to have pharmacological activities - antifungal, anti-cancer, anticoagulant. Our study designed includes in-vitro assessment and in-silico model of 13-BPB interaction to the molecular mechanism in human and its animal model, mice. Cytotoxicity assessment using MTT has shown that treatment of 13BPB on NIH-3T3 and RAW 264.7 have significant reduction in cell viability at 0.016mM and 0.08mM, respectively. Virtual database screening based on homologous compounds identified possible interaction with 15 different proteins from receptors, enzymes and transcription factors, in human and mice. Further docking analysis shows terphenyl derivatives binding affinities (pKd/pKi) are the highest with CNR1 and oestrogen receptors (ESRs).